More local scientists ID new flu antibody

Findings at Scripps similar to Burnham's

Point Loma 
For the second time in a week, local scientists have announced the discovery of a human antibody that effectively neutralizes multiple strains of the influenza virus, a development that might eventually lead to a single broad-based flu therapy and a universal vaccine.

Writing in Science Express, the online version of the journal Science, researchers at The Scripps Research Institute in La Jolla and at Crucell, a Dutch biopharmaceutical company, say they have identified a single powerful human antibody that neutralizes most strains of seasonal flu and bird flu, as well as viruses responsible for past pandemics. They dubbed it “supermantibody.”

The findings are remarkably similar to discoveries reported earlier this week by scientists at the Burnham Institute of Medical Research in La Jolla, with colleagues in Boston and Atlanta. They published their paper in the journal Nature Structural and Molecular Biology on Feb. 22.

The Scripps institute's news marks one of those rare moments when independent research programs arrive at roughly the same findings.

Both teams identified human antibodies that latch onto the stems of mushroom-shaped proteins coating flu viruses. The head of the protein, called hemagglutinin, attaches to host cells and mutates constantly, making it almost impossible to formulate a vaccine that works year after year.

“Flu vaccines tend to contain antibodies targeted at the tops of hemagglutinin,” said Ian Wilson, the Scripps study's senior investigator and a member of its Skaggs Institute for Chemical Biology.

“The heads are like red flags waving in the breeze of the immune system,” Wilson said, inviting antibodies to attack them. But because the heads of hemagglutinin change, a particular vaccine might not work. That's why researchers have to design a new flu vaccine every season.

The underlying stems, however, contain crucial machinery the virus needs to enter and infect host cells. This machinery does not mutate, leaving it vulnerable to antibodies that specifically bind to it. The result: The virus cannot fuse with a host cell and is effectively neutralized.

“This is very exciting because it marks the first step toward the Holy Grail of influenza vaccinology – the development of a durable and cross-protective universal influenza virus vaccine,” said Wilson. “Such a flu vaccine could be given to a person just once and act as a universal protectant for most subtypes of influenza, even against pandemic viruses.”

The key antibody, known as CR6261, was derived from donor blood by Crucell scientists. They initially thought CR6261 might be rare, but they have since found other donors with it. They now suspect that CR6261 might be relatively common, but that the human body doesn't generally produce enough to use it efficiently.

The research was conducted on mice. Treated with CR6261, the mice recovered from lethal doses of bird flu as late as five days after infection. Still, Wilson cautioned that more research and testing are needed, including clinical trials, before either an antibody-based flu treatment or a universal vaccine becomes available for human use.

Wilson, whose research also includes investigating the human immunodeficiency virus that causes AIDS, said the flu discovery may advance that work as well. “It's harder to find neutralizing antibodies against HIV,” he said, “but this work may help point us in new directions.”

Wilson said his team was obliged to withhold its announcement because of a media embargo mandated by the journal Science.

“Believe me, it was very frustrating. If we could have said something earlier, we would have.”